ANALGESIA PRODUCED BY BIRTH CANAL STIMULATION

我们的目标是确定出生时释放的神经递质 神经管机械刺激介导了强烈的镇痛作用， 通过这种感官刺激，以增强这种镇痛作用， 抑制神经递质的酶促分解，并确定 这些酶抑制剂是否能增强自然过程中的镇痛作用 分娩 具体目标是： 1)为了确定脑啡肽酶抑制剂thiorphan和 蛋白酶抑制剂亮抑酶肽，直接注射到脊髓 （鞘内）通过慢性导管，加强和/或延长 人工产道机械刺激产生的镇痛，以及 阿片拮抗剂纳洛酮是否能拮抗这种作用。 这 将提供证据，以证明是否阿片类药物和/或 非阿片类药物产生系统通过酶增强 抑制剂的 2)以确定相同的药物治疗是否会增强 和/或延长胎儿自然分娩期间的镇痛， 通常提供产道（例如子宫颈）的机械刺激， 他们出生了。 3)通过放射免疫测定法定量测定所选神经肽的水平 (e.g.血管活性肠肽和甲硫氨酸脑啡肽） 脊髓和脊髓节段的匀浆， 产道刺激引起子宫肌瘤。 这将提供证据， 产生镇痛作用的特定神经肽是否在 脊髓对感觉刺激的反应类似于 在分娩过程中正常发生。 最终的目标是利用，神经学和/或神经学， 这个强大的刺激神经的自然感觉系统 疼痛的症状

Our objectives are to identify the neurotransmitter(s) released by birth canal mechanostimulation that mediate(s) the powerful analgesia triggered by this sensory stimulus, to augment this analgesia pharmacologically by inhibiting enzymatic breakdown of the neurotransmitter(s), and to determine whether these enqyme-inhibitors augment analgesia during natural parturition. The specific aims are: 1) to determine whether the enkephalinase inhibitor, thiorphan, and the protease inhibitor, leupeptin, injected directly to the spinal cord (intrathecally) via chronic catheter, intensify and/or prolong the analgesia produced by artificial birth canal mechano-stimulation, and whether the opiate antagonist, naloxone, antagonizes this effect. This will provide evidence as to whether the activity of opiate and/or non-opiate analgesia-producing systems are potentiated by the enzyme inhibitors. 2) to determine whether the same pharmacological treatments intensify and/or prolong analgesia during the natural delivery of fetuses, which normally provide mechano-stimulation of the birth canal (e.g. cervix) as they are born. 3) to quantify, by radioimmunoassay, the levels of selected neuropeptides (e.g. vasoactive intestinal peptide and met-enkephalin) in superfusates of the spinal cord and homogenates of spinal cord segments, in response to analgesia-producing birth canal stimulation. This will provide evidence as to whether specific neuropeptides that produce analgesia are released in the spinal cord in response to sensory stimulation similar to that occurring normally during parturition. The ultimate goal is to utilize, pharmacologically and/or neurologically, this powerful analgesia-triggering natural sensory system for the control of pain in humans.